Maternal natural killer cells at the intersection between reproduction and mucosal immunity

Abstract

Many maternal immune cells populate the decidua, which is the mucosal lining of the uterus transformed during pregnancy. Here, abundant natural killer (NK) cells and macrophages help the uterine vasculature adapt to fetal demands for gas and nutrients, thereby supporting fetal growth. Fetal trophoblast cells budding off the forming placenta and invading deep into maternal tissues come into contact with these and other immune cells. Besides their homeostatic functions, decidual NK cells can respond to pathogens during infection, but in doing so, they may become conflicted between destroying the invader and sustaining fetoplacental growth. We review how maternal NK cells balance their double duty both in the local microenvironment of the uterus and systemically, during toxoplasmosis, influenza, cytomegalovirus, malaria and other infections that threat pregnancy. We also discuss recent developments in the understanding of NK-cell responses to SARS-Cov-2 infection and the possible dangers of COVID-19 during pregnancy.

The Pivotal Role of the Placenta in Normal and Pathological Pregnancies: A Focus on Preeclampsia, Fetal Growth Restriction, and Maternal Chronic Venous Disease

“…Trophoblast release of interleukin-15 (IL-15) seems to promote dNK maturation, and these cells promote decidual remodeling through the production of several cytokines, such as interferon-gamma (IFN-γ), vascular endothelial growth factor (VEGF), tumor necrosis factor-α (TNF-α), IL-8, and the chemokine (C-X-C motif) ligand 10 (CXCL10) [32]. Moreover, dNKs are also major mediators of the immune response against several pathogens such as toxoplasmosis or human cytomegalovirus (HCMV) [33]. Recently, three different subsets of NKs have been identified (dNK1, dNK2, and dNK3) [34].…”

Immunoendocrine Dysregulation during Gestational Diabetes Mellitus: The Central Role of the Placenta

“…Regarding NK cells, diverse comprehensive reviews have described the critical participation of NK cells, particularly decidual NK cells with CD56bright/superbright and CD16-phenotype, in pregnancy development [132,133]. However, few original articles have revised the role of these cells in GDM pathophysiology.…”

Immunity at maternal–fetal interface: KIR/HLA (Allo)recognition*

“…It is important to note that differences in the activity of mature NK cells attributed to education are not due to changes in gene expression, but rather are the result of differences in signaling. Acquisition of self MHC class I‐specific iKIRs in NK cells is an essential event of their education in order to achieve functional competence 191 . During the education, the receptors that produce the inhibitory signal shift from the NKG2A:HLA‐E system to that of KIR:HLA‐C as the NK cells mature 192 .…”